Bacterial virulence phenotypes of Escherichia coli and host susceptibility determines risk for urinary tract infections

• Published in: Science translational medicine 2017-03, Vol.9 (382)
• Main Authors: Schreiber, Henry L., Conover, Matt S., Chou, Wen-Chi, Hibbing, Michael E., Manson, Abigail L., Dodson, Karen W., Hannan, Thomas J., Roberts, Pacita L., Stapleton, Ann E., Hooton, Thomas M., Livny, Jonathan, Earl, Ashlee M., Hultgren, Scott J.
• Format: Article
• Language: English
• ISSN: 1946-6234; 1946-6242
• DOI: 10.1126/scitranslmed.aaf1283

Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in urovirulence, or the ability to infect the bladder of a mouse model of cystitis. Importantly, we found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the E. coli strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and sugar metabolism, could be used to predict subsequent mouse bladder colonization. Taken together, our findings suggest that UTI risk and outcome may be determined by complex interactions between host susceptibility and the urovirulence potential of diverse bacterial strains.